Subscribe
Phenylketonuria
Phenylketonuria Clinical Symptoms
Phenylketonuria may appear normal at birth, but symptoms usually start to appear between three to six months, with the symptoms becoming most evident at one year old. These are often manifestations of the nervous system, with prominent developmental delays in intelligence. The IQ is often lower than normal, and there may be abnormal behaviors, minor epileptic seizures, and, in a few children, increased muscle tone and hyperactive tendon reflexes. Due to insufficient melanin synthesis a few months after birth, affected children’s hair color changes from black to yellow, their skin is fair, and skin eczema is relatively common. Due to the elevated excretion of phenylacetic acid in urine and sweat, there is a distinct mouse-like urine smell.
How is phenylketonuria cured?
Phenylketonuria is an autosomal recessive genetic disease, primarily due to a mutation in the phenylalanine hydroxylase gene which leads to reduced enzymatic activity, causing the accumulation of phenylalanine and its metabolites in the body, thereby leading to this disease. The main manifestations include developmental intellectual disabilities, light skin and hair pigmentation, and a musty urine odor. Once diagnosed, immediate treatment is necessary, mainly using a low-phenylalanine formula milk. Generally, when orally administering low-phenylalanine formula milk, it is essential to monitor the phenylalanine levels in the blood. Since each patient has a different tolerance level for phenylalanine, periodic determination of blood phenylalanine concentration is required in the dietary treatment. Such patients can only be treated long-term in this way; it is not curable nor can it be completely eradicated; treatment can only alleviate the symptoms and involves long-term administration of a low-phenylalanine diet.
Can phenylketonuria be cured?
Once phenylketonuria is diagnosed, immediate treatment is necessary; the younger the age at which treatment is started, the better the prognosis. The main approach is to use a low phenylalanine formula milk for treatment. Once the blood phenylalanine concentration has decreased to the desired level, we can gradually begin adding small amounts of natural diet. For small infants, breast milk is preferred since it contains much less phenylalanine than cow's milk. For older infants, additions such as cow's milk, porridge, noodles, and eggs are acceptable, but supplements should still follow the principle of being low in protein and phenylalanine. The amount and frequency of these additions should be determined based on the phenylalanine concentration, as too high or too low levels can affect growth and development. This condition can only be managed by controlling symptoms and maintaining blood phenylalanine levels. Long-term treatment is required; it cannot be cured, only controlled.
Phenylketonuria is caused by how?
Phenylketonuria is caused by how? It is an autosomal recessive genetic disease, mainly due to a mutation in the phenylalanine hydroxylase gene, which leads to a reduction in the activity of phenylalanine hydroxylase. Phenylalanine is an essential amino acid in the human body. The phenylalanine ingested is partly used for protein synthesis, and the rest is converted into tyrosine by the action of phenylalanine hydroxylase, with only a small amount of phenylalanine being converted into phenylpyruvic acid through a minor metabolic pathway under the action of transaminase. Due to the reduced activity of phenylalanine hydroxylase, phenylalanine cannot be converted into tyrosine, resulting in an extremely high concentration of phenylalanine in the blood, cerebrospinal fluid, and tissues. Through a bypass metabolism, a large amount of phenylpyruvic acid, phenylacetic acid, phenyllactic acid, and p-hydroxyphenylacetic acid are produced. High concentrations of phenylalanine and its metabolites thus lead to brain damage. Due to the synthesis disorder of tyrosine, this also leads to symptoms such as light skin and hair pigmentation.
The pathogenesis of phenylketonuria
Phenylketonuria is an autosomal recessive genetic disorder. Phenylalanine, which is an essential amino acid required by the human body, is partly used for protein synthesis after ingestion and partly converted into tyrosine via the action of phenylalanine hydroxylase, which is necessary for the synthesis of substances such as adrenaline, melanin, and thyroxine. Phenylketonuria is mainly caused by a deficiency of phenylalanine hydroxylase, which prevents the conversion of phenylalanine to tyrosine. This leads to increased levels of phenylalanine in the blood, cerebrospinal fluid, and various tissues. Additionally, as the primary metabolic pathway is blocked, secondary metabolic pathways are enhanced. Under the action of transaminases, phenylalanine undergoes deamination to produce large quantities of phenylpyruvic acid, which is further metabolized to produce phenylacetic acid, phenyllactic acid, and p-hydroxyphenylpyruvic acid, among other byproduct metabolites. These are excreted in large amounts in the urine. The high concentration of phenylalanine and its byproduct metabolites accumulates in brain tissue, leading to damage to brain cells and resulting in a range of clinical symptoms.
Phenylketonuria Test Methods
The examination methods for phenylketonuria primarily include newborn screenings usually performed three to seven days after birth by drawing a blood sample from the heel and placing drops on specialized blood collection filter paper. Once dried, the sample is sent to a screening laboratory to determine the concentration of phenylalanine. If the phenylalanine concentration exceeds the cutoff value, further examinations and confirmatory tests are necessary, with the confirmatory test involving the measurement of phenylalanine concentration. Another method involves the analysis of urinary pterin profile, mainly used to differentiate dihydrobiopterin reductase deficiency. Additionally, gene analysis can be applied to detect mutations in genes such as phenylalanine hydroxylase, aiding in genetic diagnoses and prenatal diagnoses.
Phenylketonuria lacks what enzyme?
Phenylketonuria is an autosomal recessive genetic disorder caused by a mutation in the phenylalanine hydroxylase gene, which leads to reduced enzyme activity and the accumulation of phenylalanine and its metabolites in the body, resulting in disease. Phenylketonuria is the most common congenital disorder of amino acid metabolism, clinically characterized by developmental delays in intelligence, light pigmentation of the skin and hair, and a mousey odor to the urine. It is often due to a deficiency of phenylalanine hydroxylase.
How is phenylketonuria diagnosed?
How is phenylketonuria diagnosed? Firstly, we start with screening, which is usually done when the newborn is 3 to 7 days old by heel prick to collect peripheral blood, which is then dropped onto specialized filter paper for the determination of phenylalanine concentration. If the concentration of phenylalanine is above the cutoff value, further determination of phenylalanine concentration is conducted. The normal concentration is less than 120 umol/L. If the concentration of phenylalanine is greater than 1200 umol/L, it suggests severe phenylketonuria. Moderate levels are above 360 umol/L, and mild levels are above 120 umol/L but less than 360 umol/L. Furthermore, diagnosis can be confirmed through DNA analysis, currently available tests include screening for mutations in the phenylalanine hydroxylase gene.
Clinical symptoms of phenylketonuria
The clinical symptoms of phenylketonuria generally include normal appearance at birth, with symptoms usually appearing between three to six months, and becoming more pronounced by the age of one. The most noticeable initial symptoms involve the nervous system; delayed intellectual development is prominent, with intelligence often below normal, along with behavioral abnormalities such as hyperactivity, depression, restlessness, and withdrawal. There could be minor epileptic seizures, and in some cases, increased muscle tone or exaggerated tendon reflexes. Regarding the skin, several months after birth, due to insufficient melanin synthesis, the child’s hair changes from black to yellow, the skin appears pale, and eczema is also relatively common. Additionally, the urine and sweat contain higher levels of phenylacetic acid, which can result in a distinctive mouse-like urine odor.
What is the probability of phenylketonuria?
Phenylketonuria is an autosomal recessive genetic disorder primarily caused by mutations in the phenylalanine hydroxylase gene, leading to reduced enzyme activity and the accumulation of phenylalanine and its metabolites in the body, resulting in the disease. Phenylketonuria is the most common congenital amino acid metabolism disorder, with clinical manifestations mainly including intellectual developmental delays, light skin and hair pigmentation, and a mouse urine odor. The incidence of the disease varies by race and region. In China, the incidence of phenylketonuria is approximately 1 in 11,000, meaning that about one in 11,000 children suffers from phenylketonuria.